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PubMed This is a summary of 16 peer-reviewed journal articles Updated
Ophthalmology

The Diagnostic Detective: Confirming HSK and Spotting Imposters

At a Glance

Diagnosing Herpes Simplex Virus stromal keratitis (HSK) involves a clinical eye exam, corneal sensitivity testing, and sometimes PCR or IVCM. Ruling out imposters like Acanthamoeba or fungal infections is critical, as HSK steroid treatments can make these other conditions dangerously worse.

Diagnosing Herpes Simplex Virus (HSV) stromal keratitis (HSK) is often described as a “clinical diagnosis.” This means your doctor identifies it primarily by looking at your eye through a slit lamp (a specialized microscope) rather than relying solely on a lab test [1][2]. However, because HSK can look like several other serious eye conditions, confirming the diagnosis—and ruling out “imposters”—is critical for saving your vision.

Tools for a Clearer Picture

While the slit lamp is the first line of defense, other technologies help when the diagnosis is uncertain:

  • PCR (Polymerase Chain Reaction): This lab test looks for the genetic material of the virus. It is very accurate but is most effective when you have active sores on the surface of the eye [1][3].
  • IVCM (In Vivo Confocal Microscopy): Think of this as a “live biopsy.” It is a non-invasive imaging tool that allows doctors to see your cornea at a cellular level. It is especially useful for finding “imposters” like parasites or fungi that are hidden deep in the cornea [1][4].
  • Sensitivity Testing: Doctors often use a fine piece of thread or a puff of air to check your corneal sensation. Because HSV travels through nerves, a “numb” eye is a classic sign of HSK [1][5].

The “Imposters”: What Else Could It Be?

The greatest risk in treating HSK is misdiagnosing another infection. The steroids used to treat HSK can act like “fertilizer” for fungi or parasites, making those infections much worse [6].

Imposter Key Differentiating Signs
Acanthamoeba Often seen in contact lens wearers. The pain is usually “out of proportion” (much worse than the eye looks). Doctors may see radial keratoneuritis (inflamed nerves) [7][8].
Fungal Keratitis Usually follows an injury with “organic” material (like a tree branch). It often has “feathery” edges rather than the smooth cloudiness of HSK [9][10].
Drug Toxicity Certain eye drop preservatives, specifically Polyquaternium-1 (PQ-1), can cause pseudodendrites. These look almost exactly like HSV surface lesions but are actually a toxic reaction to the drops [11][12].

Checklist: When to Question the Diagnosis

If your eye is not improving after a week or two of standard HSK treatment (antivirals and steroids), it is time to reassess. Here is a checklist of factors that should be discussed with your care team:

  • [ ] Contact Lens History: If you wear lenses, have you ever used tap water to clean them? (Increases risk of Acanthamoeba) [13].
  • [ ] Pain Levels: Is your pain deep, throbbing, and severe? (Possible sign of Acanthamoeba) [7].
  • [ ] Medication Review: Are you using artificial tears or glaucoma drops preserved with Polyquaternium-1? (Possible toxic “pseudodendrite”) [11].
  • [ ] Injury History: Did your symptoms start after a scratch from a plant or soil? (Increases risk of fungal infection) [9].
  • [ ] No Response to Steroids: If the “haze” in your eye gets worse or doesn’t budge after starting steroids, an imposter or a co-infection must be ruled out using IVCM or PCR [14][15].

Resistant HSK

Sometimes the diagnosis is correct, but the HSK is “refractory” (resistant to treatment). In these cases, doctors may move beyond standard drops to oral or intravenous antivirals or add immunomodulators like cyclosporine to calm the immune system without the side effects of high-dose steroids [15][16].

Return to the Home Page.

Common questions in this guide

How do doctors test for Herpes Simplex Virus in the eye?
Doctors primarily use a specialized microscope called a slit lamp to examine your eye. They may also test your eye's sensitivity, or use advanced tests like a PCR swab or in vivo confocal microscopy (IVCM) to look closer if the diagnosis is unclear.
What are the common infections that mimic HSK?
HSK can look very similar to other serious eye conditions, including Acanthamoeba from contact lens use, fungal infections from eye injuries, and toxic reactions to certain eye drops. It is vital to rule these out because standard HSK treatments can make fungal or parasite infections worse.
Why does my doctor check if my eye is numb?
The herpes simplex virus travels through and damages the nerves in your cornea, which often leads to reduced feeling or a completely numb eye. Checking your eye's sensitivity helps doctors determine if HSV is the likely cause of your symptoms.
Could my eye drops be causing symptoms that look like HSK?
Yes, certain preservatives in artificial tears or glaucoma drops, specifically Polyquaternium-1, can cause a toxic reaction. This creates surface lesions called pseudodendrites that look almost exactly like a herpes simplex virus infection under the microscope.
What should I do if my HSK is not improving with treatment?
If your eye is not getting better after a week or two of using standard antivirals and steroids, speak with your eye doctor immediately. They may need to reassess the diagnosis to check for an imposter infection, or adjust your medication for resistant HSK.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Have you performed a corneal sensitivity test to see if my eye is numb?
  2. 2.Is there any chance this is an 'imposter' like Acanthamoeba or a fungal infection, especially since it isn't clearing up?
  3. 3.Would In Vivo Confocal Microscopy (IVCM) or a PCR test help confirm the diagnosis?
  4. 4.Do any of the eye drops I am currently using contain the preservative Polyquaternium-1?
  5. 5.Are there signs of 'radial keratoneuritis' (nerve inflammation) that might point toward Acanthamoeba instead of HSV?

Questions For You

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References

References (16)
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    Infectious keratitis: A review.

    Cabrera-Aguas M, Khoo P, Watson SL

    Clinical & experimental ophthalmology 2022; (50(5)):543-562 doi:10.1111/ceo.14113.

    PMID: 35610943
  2. 2

    Herpes simplex keratitis: challenges in diagnosis and clinical management.

    Azher TN, Yin XT, Tajfirouz D, et al.

    Clinical ophthalmology (Auckland, N.Z.) 2017; (11()):185-191 doi:10.2147/OPTH.S80475.

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  3. 3

    Diagnostic performance of real-time quantitative PCR in tear samples in various subtypes of herpes simplex keratitis.

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    Journal of clinical microbiology 2023; (61(12)):e0088523 doi:10.1128/jcm.00885-23.

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    Dendritic cells in the cornea during Herpes simplex viral infection and inflammation.

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    PMID: 29129651
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    A Patient With Recurrent Immune Stromal Keratitis and Adherence Challenges.

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    Federal practitioner : for the health care professionals of the VA, DoD, and PHS 2022; (39(10)):403-405 doi:10.12788/fp.0323.

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    Stromal Keratitis After Varicella in Children.

    Denier M, Gabison E, Sahyoun M, et al.

    Cornea 2020; (39(6)):680-684 doi:10.1097/ICO.0000000000002281.

    PMID: 32118671
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    Differentiation of acanthamoeba keratitis from other non-acanthamoeba keratitis: Risk factors and clinical features.

    Alreshidi SO, Vargas JM, Ahmad K, et al.

    PloS one 2024; (19(3)):e0299492 doi:10.1371/journal.pone.0299492.

    PMID: 38470877
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    Acanthamoeba keratitis - Clinical signs, differential diagnosis and treatment.

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    Journal of current ophthalmology 2019; (31(1)):16-23 doi:10.1016/j.joco.2018.09.008.

    PMID: 30899841
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    Corneal infection in Shandong peninsula of China: a 10-year retrospective study on 578 cases.

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    Observation of Retrocorneal Plaques in Patients With Infectious Keratitis Using Anterior Segment Optical Coherence Tomography.

    Takezawa Y, Suzuki T, Shiraishi A

    Cornea 2017; (36(10)):1237-1242 doi:10.1097/ICO.0000000000001286.

    PMID: 28704321
  11. 11

    Dendritiform Keratopathy Associated with Exposure to Polyquarternium-1, a Common Ophthalmic Preservative.

    Matoba AY, Peterson JR, Wilhelmus KR

    Ophthalmology 2016; (123(3)):451-6.

    PMID: 26686962
  12. 12

    Anti-glaucoma agents-induced pseudodendritic keratitis presumed to be herpetic simplex keratitis: a clinical case series.

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    Scientific reports 2021; (11(1)):21443 doi:10.1038/s41598-021-01073-0.

    PMID: 34728756
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    Case series: Delayed diagnoses of Acanthamoeba keratitis.

    Lee MJ, Srikumaran D, Zafar S, et al.

    American journal of ophthalmology case reports 2020; (19()):100778 doi:10.1016/j.ajoc.2020.100778.

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    Diagnostic Evaluation of Co-Occurrence of Acanthamoeba and Fungi in Keratitis: A Preliminary Report.

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    Role of Intravenous Acyclovir in Treatment of Herpes Simplex Virus Stromal Keratitis with Ulceration: A Review of 2 Cases.

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    Evaluation of safety and efficacy of cyclosporine-A eye drops in herpetic stromal keratitis: a prospective randomized clinical trial.

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This page is for informational purposes only and does not replace professional medical advice. Always consult your ophthalmologist or eye care provider about your specific symptoms and diagnosis.

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